Density functional evaluation and a feasibility study of intramolecular thione-thiol tautomerization

Abstract

Performance of various density functionals for use in geometry and energetics calculation of thiocarbonyl systems is evaluated. The three biologically significant systems such as 2-methyl-3-thiosemicarbazide, 1-acetyl-2-thiohydantoin and bornane-2-thione are selected for the geometry analysis. Energy of tautomerization of thioacetone and enthalpy of formation of 2thiohydantoin are considered for analyzing the performance in energetics. Minnesota functionals such as M05-2X, M06-2X and range separated hybrid functional wB97 give best results in both geometry and energetics calculations. Studies on basis set effect showed reliable performance by 6-31 1 G* and 6-3111G** over higher basis sets. Feasibility of tautomerization in the aforementioned thiones has been investigated using the best performing density functionals.The proposed thione-thiol tautomerization step during PPC-DC catalyzed decarboxylation reaction has also been investigated and the computed high energy barrier shows less feasibility of the reaction. K E Y W O R D S basis set effect, calibration, density functionals, tautomerization, thiocarbonyl systems 1 | I N T R O D U C T I O NThiocarbonyl compounds are fascinating molecules with wide range of biological activities. [1][2][3] Tautomerization in thiocarbonyl systems, in particular, has been found to be one of the significant steps in certain enzymatic reactions and in many physiological processes. [4][5][6][7][8] The studies that detail the importance of thione moiety in antithyroid agents and the effect of thione-thiol tautomerism on peroxidasecatalysed oxidation reactions and 4 0 -phosphopantothenoylcysteine decarboxylase (PPC-DC) catalyzed decarboxylation reaction were reported. [7,8] There were reports that also show the tautomerization of thiobases such as thiouracil and thiocytosine which are the constituents of t-RNA species. [4] The significance of thione-thiol tautomerism in these physiological processes demands a detailed study of its energetics. [9,10] Density functional theory (DFT) has become a powerful and time effective method for the calculation of electronic structure and other molecular properties nowadays. [11][12][13][14][15][16] Wide application of DFT methods evinces its unparallel impact on quantum mechanics to solve challenging problems in chemistry. Various DFT methods differ in their exchange-correlation functionals and this difference makes the best functional for one application often not the best for the other. [17] Therefore, the selection of a density functional from a plethora of reported exchange correlation functionals for a particular chemical problem becomes essential. Several such calibration studies have been reported. [18][19][20][21][22][23][24][25][26] Methods such as BP86 and B3LYP were found to perform well for the analysis of intermediate and transition state structures and the relative energy calculations of chemical processes. [21] However, our initial studies using B3LYP/6-31 1 G* produced a contradictory result for the geometry of simple carbonyl sys...